Managing a portfolio of corporate venture units : challenges in achieving within-unit focus and between-unit coordination

Principal Topic: There is increasing recognition that the organizational configurations of corporate venture units should depend on the types of ventures the unit seeks to develop (Burgelman, 1984; Hill and Birkinshaw, 2008). Distinction have been made between internal and external as well as exploitative versus explorative ventures (Hill and Birkinshaw, 2008; Narayan et al., 2009; Schildt et al., 2005). Assuming that firms do not want to limit themselves to a single type of venture, but rather employ a portfolio of ventures, the logical consequence is that firms should employ multiple corporate venture units. Each venture unit tailor-made for the type of venture it seeks to develop. Surprisingly, there is limited attention in the literature for the challenges of managing multiple corporate venture units in a single firm. Maintaining multiple venture units within one firm provides easier access to funding for new ideas (Hamel, 1999). It allows for freedom and flexibility to tie the organizational systems (Rice et al., 2000), autonomy (Hill and Rothaermel, 2003), and involvement of management (Day, 1994; Wadwha and Kotha, 2006) to the requirements of the individual ventures. Yet, the strategic objectives of a venture may change when uncertainty around the venture is resolved (Burgelman, 1984). For example, firms may decide to spin-in external ventures (Chesbrough, 2002) or spun-out ventures that prove strategically unimportant (Burgelman, 1984). This suggests that ventures might need to be transferred between venture units, e.g. from a more internally-driven corporate venture division to a corporate venture capital unit. Several studies suggested that ventures require different managerial skills across their phase of development (Desouza et al., 2007; O'Connor and Ayers, 2005; Kazanjian and Drazin, 1990; Westerman et al., 2006). To facilitate effective transfer between venture units and manage the overall venturing process, it is important that firms set up and manage integrative linkages. Integrative linkages provide synergies and coordination between differentiated units (Lawrence and Lorsch, 1967). Prior findings pointed to the important role of senior management (Westerman et al., 2006; Gilbert, 2006) and a shared organizational vision (Burgers et al., 2009) to coordinate venture units with mainstream businesses. We will draw on these literatures to investigate the key question of how to integratively manage multiple venture units. ---------- Methodology/Key Propositions: In order to seek an answer to the research question, we employ a case study approach that provides unique insights into how firms can break up their venturing process. We selected three Fortune 500 companies that employ multiple venturing units, IBM, Royal Dutch/ Shell and Nokia, and investigated and compared their approaches. It was important that the case companies somewhat differed in the type of venture units they employed as well as the way they integrate and coordinate their venture units. The data are based on extensive interviews and a variety of internal and external company documents to triangulate our findings (Eisenhardt, 1989). The key proposition of the article is that firms can best manage their multiple venture units through an ambidextrous design of loosely coupled units. This provides venture units with sufficient flexibility to employ organizational configurations that best support the type of venture they seek to develop, as well as provides sufficient integration to facilitate smooth transfer of ventures between venture units. Based on the case findings, we develop a generic framework for a new way of managing the venturing process through multiple corporate venture units. ---------- Results and Implications: One of our main findings is that these firms tend to organize their venture units according to phases in the venture development process. That is, they tend to have venture units aimed at incubation of venture ideas as well as units aimed more at the commercialization of ventures into a new business unit for the firm or a start-up. The companies in our case studies tended to coordinate venture units through integrative management skills or a coordinative venture unit that spanned multiple phases. We believe this paper makes two significant contributions. First, we extend prior venturing literature by addressing how firms manage a portfolio of venture units, each achieving different strategic objectives. Second, our framework provides recommendations on how firms should manage such an approach towards venturing. This helps to increase the likelihood of success of their venturing programs.

HtrA, RseP, and Tsp do not elicit a pathology related serum IgG response during sexually transmitted infection with Chlamydia trachomatis

Chlamydia trachomatis sexually transmitted infection can cause serious reproductive morbidities. This study determined the prevalence of serum IgG response to C. trachomatis putative stress response proteins in females to test for an association with genital tract pathology. There was no significant association of serum IgG to HtrA, Tsp, or RseP with infection or pathology. cHSP60 serum IgG prevalence was significantly associated with infection compared to negative (infertile) controls (p = 0.002), but not with upper genital tract pathology. Serum IgG1-4 antibody subclasses reactive with the antigens was not significantly different between cohorts, although different responses to each antigen were detected.

Protrusion I

Protrusion I is a self-portrait bust, rendered with a high degree of naturalism. The work depicts a male subject with a bulbous white form projecting from it nasal and oral orifices. The work forms part of the artist’s ongoing self-portraiture project, in which the tensions between objectivity and subjectivity that pervade the self-portrait as a genre are cross referenced with the notions of materiality and interiority integral to the language of sculpture. The iconography of the work parodies the connection between amorphous form and artistic subjectivity in the history of sculpture. The dough-like forms that emerge from the figure thus refer to a sense of ‘inner life’ while also operating as more analytical projections of the cavities of the bust – areas of the where the mimetic program are necessarily suspended. The result is a figure that appears to be in a state of resigned suffocation. The work was selected for the 2005 National Sculpture Prize and Exhibition at the National Gallery of Australia in Canberra. The work was later included in the group show Crash (and other earthy pleasures) at the Lawrence Wilson Art Gallery at the University of Western Australia in Perth.

Libr@ries : changing information space and practice

This volume examines the social, cultural, and political implications of the shift from traditional forms of print-based libraries to the delivery of online information in educational contexts. Despite the central role of libraries in literacy and learning, research of them has, in the main, remained isolated within the disciplinary boundaries of information and library science. By contrast, this book problematizes and thereby mainstreams the field. It brings together scholars from a wide range of academic fields to explore the dislodging of library discourse from its longstanding apolitical, modernist paradigm. Collectively, the authors interrogate the presuppositions of current library practice and examine how library as place and library as space blend together in ways that may be both complementary and contradictory. Seeking a suitable term to designate this rapidly evolving and much contested development, the editors devised the word “libr@ary,” and use the term arobase to signify the conditions of formation of new libraries within contexts of space, knowledge, and capital.

Large margin vector quantization

In this paper we describe the Large Margin Vector Quantization algorithm (LMVQ), which uses gradient ascent to maximise the margin of a radial basis function classifier. We present a derivation of the algorithm, which proceeds from an estimate of the class-conditional probability densities. We show that the key behaviour of Kohonen's well-known LVQ2 and LVQ3 algorithms emerge as natural consequences of our formulation. We compare the performance of LMVQ with that of Kohonen's LVQ algorithms on an artificial classification problem and several well known benchmark classification tasks. We find that the classifiers produced by LMVQ attain a level of accuracy that compares well with those obtained via LVQ1, LVQ2 and LVQ3, with reduced storage complexity. We indicate future directions of enquiry based on the large margin approach to Learning Vector Quantization.

Crosstalk between developmental and tumour-specific signalling pathways : kallikrein-related serine peptidases and nodal in prostrate cancer

Prostate cancer is an important male health issue. The strategies used to diagnose and treat prostate cancer underscore the cell and molecular interactions that promote disease progression. Prostate cancer is histologically defined by increasingly undifferentiated tumour cells and therapeutically targeted by androgen ablation. Even as the normal glandular architecture of the adult prostate is lost, prostate cancer cells remain dependent on the androgen receptor (AR) for growth and survival. This project focused on androgen-regulated gene expression, altered cellular differentiation, and the nexus between these two concepts. The AR controls prostate development, homeostasis and cancer progression by regulating the expression of downstream genes. Kallikrein-related serine peptidases are prominent transcriptional targets of AR in the adult prostate. Kallikrein 3 (KLK3), which is commonly referred to as prostate-specific antigen, is the current serum biomarker for prostate cancer. Other kallikreins are potential adjunct biomarkers. As secreted proteases, kallikreins act through enzyme cascades that may modulate the prostate cancer microenvironment. Both as a panel of biomarkers and cascade of proteases, the roles of kallikreins are interconnected. Yet the expression and regulation of different kallikreins in prostate cancer has not been compared. In this study, a spectrum of prostate cell lines was used to evaluate the expression profile of all 15 members of the kallikrein family. A cluster of genes was co-ordinately expressed in androgenresponsive cell lines. This group of kallikreins included KLK2, 3, 4 and 15, which are located adjacent to one another at the centromeric end of the kallikrein locus. KLK14 was also of interest, because it was ubiquitously expressed among the prostate cell lines. Immunohistochemistry showed that these 5 kallikreins are co-expressed in benign and malignant prostate tissue. The androgen-regulated expression of KLK2 and KLK3 is well-characterised, but has not been compared with other kallikreins. Therefore, KLK2, 3, 4, 14 and 15 expression were all measured in time course and dose response experiments with androgens, AR-antagonist treatments, hormone deprivation experiments and cells transfected with AR siRNA. Collectively, these experiments demonstrated that prostatic kallikreins are specifically and directly regulated by the AR. The data also revealed that kallikrein genes are differentially regulated by androgens; KLK2 and KLK3 were strongly up-regulated, KLK4 and KLK15 were modestly up-regulated, and KLK14 was repressed. Notably, KLK14 is located at the telomeric end of the kallikrein locus, far away from the centromeric cluster of kallikreins that are stimulated by androgens. These results show that the expression of KLK2, 3, 4, 14 and 15 is maintained in prostate cancer, but that these genes exhibit different responses to androgens. This makes the kallikrein locus an ideal model to investigate AR signalling. The increasingly dedifferentiated phenotype of aggressive prostate cancer cells is accompanied by the re-expression of signalling molecules that are usually expressed during embryogenesis and foetal tissue development. The Wnt pathway is one developmental cascade that is reactivated in prostate cancer. The canonical Wnt cascade regulates the intracellular levels of β-catenin, a potent transcriptional co-activator of T-cell factor (TCF) transcription factors. Notably, β-catenin can also bind to the AR and synergistically stimulate androgen-mediated gene expression. This is at the expense of typical Wnt/TCF target genes, because the AR:β-catenin and TCF:β-catenin interactions are mutually exclusive. The effect of β-catenin on kallikrein expression was examined to further investigate the role of β-catenin in prostate cancer. Stable knockdown of β-catenin in LNCaP prostate cancer cells attenuated the androgen-regulated expression of KLK2, 3, 4 and 15, but not KLK14. To test whether KLK14 is instead a TCF:β-catenin target gene, the endogenous levels of β-catenin were increased by inhibiting its degradation. Although KLK14 expression was up-regulated by these treatments, siRNA knockdown of β-catenin demonstrated that this effect was independent of β-catenin. These results show that β-catenin is required for maximal expression of KLK2, 3, 4 and 15, but not KLK14. Developmental cells and tumour cells express a similar repertoire of signalling molecules, which means that these different cell types are responsive to one another. Previous reports have shown that stem cells and foetal tissues can reprogram aggressive cancer cells to less aggressive phenotypes by restoring the balance to developmental signalling pathways that are highly dysregulated in cancer. To investigate this phenomenon in prostate cancer, DU145 and PC-3 prostate cancer cells were cultured on matrices pre-conditioned with human embryonic stem cells (hESCs). Soft agar assays showed that prostate cancer cells exposed to hESC conditioned matrices had reduced clonogenicity compared with cells harvested from control matrices. A recent study demonstrated that this effect was partially due to hESC-derived Lefty, an antagonist of Nodal. A member of the transforming growth factor β (TGFβ) superfamily, Nodal regulates embryogenesis and is re-expressed in cancer. The role of Nodal in prostate cancer has not previously been reported. Therefore, the expression and function of the Nodal signalling pathway in prostate cancer was investigated. Western blots confirmed that Nodal is expressed in DU145 and PC-3 cells. Immunohistochemistry revealed greater expression of Nodal in malignant versus benign glands. Notably, the Nodal inhibitor, Lefty, was not expressed at the mRNA level in any prostate cell lines tested. The Nodal signalling pathway is functionally active in prostate cancer cells. Recombinant Nodal treatments triggered downstream phosphorylation of Smad2 in DU145 and LNCaP cells, and stably-transfected Nodal increased the clonogencity of LNCaP cells. Nodal was also found to modulate AR signalling. Nodal reduced the activity of an androgen-regulated KLK3 promoter construct in luciferase assays and attenuated the endogenous expression of AR target genes including prostatic kallikreins. These results demonstrate that Nodal is a novel example of a developmental signalling molecule that is reexpressed in prostate cancer and may have a functional role in prostate cancer progression. In summary, this project clarifies the role of androgens and changing cellular differentiation in prostate cancer by characterising the expression and function of the downstream genes encoding kallikrein-related serine proteases and Nodal. Furthermore, this study emphasises the similarities between prostate cancer and early development, and the crosstalk between developmental signalling pathways and the AR axis. The outcomes of this project also affirm the utility of the kallikrein locus as a model system to monitor tumour progression and the phenotype of prostate cancer cells.

Monte Carlo modelling of X-ray absorptiometry and its application to body composition studies

This thesis applies Monte Carlo techniques to the study of X-ray absorptiometric methods of bone mineral measurement. These studies seek to obtain information that can be used in efforts to improve the accuracy of the bone mineral measurements. A Monte Carlo computer code for X-ray photon transport at diagnostic energies has been developed from first principles. This development was undertaken as there was no readily available code which included electron binding energy corrections for incoherent scattering and one of the objectives of the project was to study the effects of inclusion of these corrections in Monte Carlo models. The code includes the main Monte Carlo program plus utilities for dealing with input data. A number of geometrical subroutines which can be used to construct complex geometries have also been written. The accuracy of the Monte Carlo code has been evaluated against the predictions of theory and the results of experiments. The results show a high correlation with theoretical predictions. In comparisons of model results with those of direct experimental measurements, agreement to within the model and experimental variances is obtained. The code is an accurate and valid modelling tool. A study of the significance of inclusion of electron binding energy corrections for incoherent scatter in the Monte Carlo code has been made. The results show this significance to be very dependent upon the type of application. The most significant effect is a reduction of low angle scatter flux for high atomic number scatterers. To effectively apply the Monte Carlo code to the study of bone mineral density measurement by photon absorptiometry the results must be considered in the context of a theoretical framework for the extraction of energy dependent information from planar X-ray beams. Such a theoretical framework is developed and the two-dimensional nature of tissue decomposition based on attenuation measurements alone is explained. This theoretical framework forms the basis for analytical models of bone mineral measurement by dual energy X-ray photon absorptiometry techniques. Monte Carlo models of dual energy X-ray absorptiometry (DEXA) have been established. These models have been used to study the contribution of scattered radiation to the measurements. It has been demonstrated that the measurement geometry has a significant effect upon the scatter contribution to the detected signal. For the geometry of the models studied in this work the scatter has no significant effect upon the results of the measurements. The model has also been used to study a proposed technique which involves dual energy X-ray transmission measurements plus a linear measurement of the distance along the ray path. This is designated as the DPA( +) technique. The addition of the linear measurement enables the tissue decomposition to be extended to three components. Bone mineral, fat and lean soft tissue are the components considered here. The results of the model demonstrate that the measurement of bone mineral using this technique is stable over a wide range of soft tissue compositions and hence would indicate the potential to overcome a major problem of the two component DEXA technique. However, the results also show that the accuracy of the DPA( +) technique is highly dependent upon the composition of the non-mineral components of bone and has poorer precision (approximately twice the coefficient of variation) than the standard DEXA measurements. These factors may limit the usefulness of the technique. These studies illustrate the value of Monte Carlo computer modelling of quantitative X-ray measurement techniques. The Monte Carlo models of bone densitometry measurement have:- 1. demonstrated the significant effects of the measurement geometry upon the contribution of scattered radiation to the measurements, 2. demonstrated that the statistical precision of the proposed DPA( +) three tissue component technique is poorer than that of the standard DEXA two tissue component technique, 3. demonstrated that the proposed DPA(+) technique has difficulty providing accurate simultaneous measurement of body composition in terms of a three component model of fat, lean soft tissue and bone mineral,4. and provided a knowledge base for input to decisions about development (or otherwise) of a physical prototype DPA( +) imaging system. The Monte Carlo computer code, data, utilities and associated models represent a set of significant, accurate and valid modelling tools for quantitative studies of physical problems in the fields of diagnostic radiology and radiography.

Use of electronic travel diaries and vehicle instrumentation packages in the year 2000 : Atlanta Regional Household Travel Survey

The Georgia Institute of Technology is currently performing research that will result in the development and deployment of three instrumentation packages that allow for automated capture of personal travel-related data for a given time period (up to 10 days). These three packages include: A handheld electronic travel diary (ETD) with Global Positioning System (GPS) capabilities to capture trip information for all modes of travel; A comprehensive electronic travel monitoring system (CETMS), which includes an ETD, a rugged laptop computer, a GPS receiver and antenna, and an onboard engine monitoring system, to capture all trip and vehicle information; and a passive GPS receiver, antenna, and data logger to capture vehicle trips only.